1. Field of the Invention
This invention relates to articles and methods for storage and transport of biogenic fluids such as blood, blood fractions, intravenous feeding solutions and liquid phase-delivered drugs.
2. Description of the Prior Art
Biogenic fluids include blood, blood fractions, intravenous feeding solutions and liquid phase-delivered drugs and are normally introduced to a patient intravenously or intramuscularly. All biogenic fluids must be stored and transported with extreme care, to avoid contamination and physical and chemical breakdown of the fluid.
The prior art is largely concerned with storage and transport of blood and blood fractions.
Use of polymers, having negatively charged monomer constituent elements, to store blood, to thereby minimize blood clotting, is disclosed by U.S. Pat. No. 3,633,578.
U.S. Pat. No. 3,723,754, French patent publication 2,089,788 and Japanese application Ser. No. 45/75116, the convention application from which the U.S. and French applications derive their priority dates, disclose a device for blood storage and for dynamic flow of blood therethrough, fabricated as an electret having a stable heterocharge and constructed so the negative charge bearing surface of the electret contacts the blood, to reduce clotting as the blood touches the device. These references teach that the device may be constructed of polyvinylidene fluoride.
Two problems plague flexible plastics known for use in storing and handling biogenic fluids such as blood. First, flexible plastics used to store biogenic fluids contain leachables which enter the fluid from the container (made of the flexible plastic) in which the fluid is stored. It is not known whether the leachables adversely affect the fluid per se, however, it is postulated that they may have extremely undesirable effects on the patient into whom the fluid is introduced. Second, in the case of blood, red blood cells deteriorate upon contact with many materials in which biogenic fluids, including blood, are currently stored; this deterioration phenomenon is "red cell hemolysis." This manifests itself as cell rupture and results in release of hemoglobin from the red cells into the blood plasma, rendering the blood incapable of carrying oxygen.
The relationship, if any, between these two problems is unknown.
Concerning leachables, plasticizers such as Di-2-ethylhexyl phthalate (DEHP) form up to 40% of the dry weight of flexible plastic currently used to store and transport biogenic fluids. These plasticizers leach from flexible plastic into any blood or blood components stored in the plastic. This has been reported in the New England Journal of Medicine, Volume 292, No. 8, "Identification and Measurement of Plasticizer in Neonatal Tissues After Umbilical Catheters and Blood Products," Feb. 20, 1975, and in the Journal of Transfusion, Volume 16, No. 4, "Fate in Humans of the Plasticizers Di-2-Ethylhexyl Phthalate Arising from Transfusion of Platelets Stored in Vinyl Plastic Bags," July/August 1976.
Two adverse effects of these plasticizers have been identified: When blood containing DEHP is transfused into a pregnant rat, the DEHP migrates from the mother into the fetus. This produces a teratogenic effect on the unborn fetus; DEHP may have the same effect on humans. See Journal of Pharmaceutical Sciences, Volume 64, No. 8, "Maternal-Fetal Transfer of 14C-Di-2-Ethylhexyl Phthalate and 14-C-Diethyl Phthalate in Rats," August 1975. Additionally, DEHP, when administered via injection, damages rats' lungs. From this researchers have postulated that DEHP might be the cause of "shock lung," a frequent cause of death among humans receiving massive blood transfusions during surgery. See Chemical & Engineering News, June 9, 1975, page 5.
Red cell hemolysis during blood storage is recognized in U.S. Pat. No. 3,257,072, which discloses apparatus and a method for storing blood. The '072 method utilizes a container having two storage volumes formed of fluorinated ethylene propylene or of polytetrafluoroethylene. These materials yield only a translucent storage container; they generally do not require plasticizers to be flexible. Fluorocarbon polymers, such as those disclosed in the '072 patent, are known to exhibit superior resistance to chemical and biological attack. See the Handbook of Biomedical Plastics, Pasedena Technology Press, copyright 1971.
A consideration in choosing materials for storage and transport of biogenic fluids is the sterilizability of a candidate material.
The preferred commercial method of sterilizing articles made of thin plastic film used for storage and transport of biogenic fluid utilizes ethylene oxide. Sterilization is performed at room temperature and at approximately atmospheric pressure. The fluid storage and transport articles made of the plastic film are sealed and maintained in an ethylene oxide environment for a time which is a function of the film material. The articles are then removed from the ethylene oxide environment and taken to a storage area where they are maintained under clean conditions until free of ethylene oxide and by-products; this takes from two (2) to three (3) weeks. Lengthy storage is necessary to allow the ethylene oxide to escape from the articles interior through the film and to outgas from the film itself.
Theory of gas transport through plastic films is not well enough developed to allow accurate prediction of rate of transport of a particular gas, such as ethylene oxide, through film. A leading reference on gas transport through films is The Science and Technology of Polymeric Films published by Wiley-Interscience, Inc., copyright 1971. This reference discloses that (1) polymer films act as barriers to gas if the films are free of macroscopic defects such as pinholes and cracks and (2) gas transport through polymer films is a function of the morphology and molecular topology of the polymer and of the chemical compositions of the polymer and the gas of interest. This reference hypothesizes that two distinct mechanisms contribute to such gas transport. The two hypothesized mechanisms are (1) gas migration via microscopic and smaller pores through the polymer film and (2) gas dissolution into the polymer film at the film surface followed by gas diffusion through the film due to gas concentration gradient therewithin.
Hypotheses such as the foregoing represent the leading edge of gas transport theory; the theory is not sufficiently advanced to permit qualitative or quantitative selection of polymers providing maximum transport rate of a given gas. Consequently, there is no adequate theory to permit qualitative or quantitative selection of plastics for biogenic fluid storage based on time required for gas sterilization of an article made of a particular plastic.
Patents which disclose various polymers and methods of making same, which may be of background interest, are U.S. Pat. Nos. 2,968,649; 3,193,539; 3,790,540 and 3,857,827. None of these disclose apparatus or methods for storage or transport of biogenic fluids.